Erythromycins (A) through (D), represented by formula (E),
______________________________________ ##STR2## Erythromycin R.sup.a R.sup.b ______________________________________ (A) --OH --CH.sub.3 (B) --H --CH.sub.3 (C) --OH --H (D) --H --H ______________________________________
are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infections.
A recently developed erythromycin derivative having the formula: ##STR3## has been described as a prokinetic agent having use in the treatment of gastrointestinal motility disorders (P. A. Lartey, et al., J. Med. Chem., 38 (1793-1798 (1995); R. Faghih, et al., PCT application WO 9313780, published Jul. 22, 1993). The preparation of the above compound requires the preparation of the intermediate compound, namely, 4"-deoxyerythromycin B.
In the process for the deoxygenation of erythromycins, the 4"-hydroxyl group is initially derivatized as a thiocarbamate. This requires prior protection of the more reactive 2'-hydroxyl group as the acetate. Deoxygenation at the 4"-position of erythromycin with the aid of dialkyl phosphites and hypophosphorous acid has been reported by Barton, S., et al., J. Org. Chem, 58:6838-42 (1993).
A process for deoxygenation of the 4"-hydroxy group of the erythromycins A and B by the treatment of starting materials, 2'-O-acetyl-4"-imidazolylthiocarbamoyl-erythromycins A and B using hypophosphorus acid in the presence of a radical initiator 4,4'-azobis-(4-cyanovaleric acid) (ACVA) is described in a commonly-owned co-pending U.S. patent application Ser. No. 08/785,451.
However, there still exists a need for an improved and more efficient method for the synthesis and manufacture of the 4"-deoxygenated erythromycin derivatives to provide cheaper and more widely available desired prokinetic agents.